The proposed studies are aimed at defining the precise role of products coded for by genes associated with the major murine histocompatibility complex (H-2) in immunity to syngeneic tumors. The experimental model for these studies will consist of methylchol anthrene-induced fibrosarcomas derived in congenic, congenic-recombinant and congenic mutant inbred strains of mice as well as in F1 hybrids appropriate for analysis of the role of H-2 subloci in tumor-specific immunity. These tumors have previously been characterized with respect to in vitro growth, lethality, immunogenicity and alloantigenicity in syngeneic and congenic strains; moreover, the relative alloantigen content of many of these tumors has been determined by serological and cellular assays. Analysis of the immune response to syngeneic tumors will include further resolution of the specificity of hyperimmune effector peritoneal exudate cells (HYPEC) from syngeneic hosts. Systematic probation of HYPEC will be performed in order to exclude or include possible participation of respectively, non-T or T-lymphocytes (in the in vitro tumor-specific cytolytic response). HYPEC directed against TSTA-like tumor target structures will be examined for possible H-2 restriction. Assessment of the TSTA-H-2 intramembrane relationship on methylcholanthrene tumors will be accomplished by immunoprecipitation (with monoclonal H-2 antibodies) and chemical analysis. TSTA-directed serological reagents will be developed through several novel approaches. Development of anti-idiotypic antibodies against syngeneic HYPEC displaying TSTA-like specificity will reveal whether TSTA Detected in vitro by cytolytic effectors are the same as serologically detected TSTA. Genetic studies will be performed to determine whether expression of TSTA or in vivo resistance and/or susceptibility to MCA tumors is MHC associated.